Maternal RNF114-mediated target substrate degradation regulates zygotic genome activation in mouse embryos.

Zygotic genomic activation (ZGA) is a landmark event in the maternal-to-zygotic transition (MZT), and the regulation of ZGA by maternal factors remains to be elucidated. In this study, the depletion of maternal ring finger protein 114 (RNF114), a ubiquitin E3 ligase, led to developmental arrest of two-cell mouse embryos. Using immunofluorescence and transcriptome analysis, RNF114 was proven to play a crucial role in major ZGA. To study the underlying mechanism, we performed protein profiling in mature oocytes and found a potential substrate for RNF114, chromobox 5 (CBX5), ubiquitylation and degradation of which was regulated by RNF114. The overexpression of CBX5 prevented embryonic development and impeded major ZGA. Furthermore, TAB1 was abnormally accumulated in mutant two-cell embryos, which was consistent with the result of in vitro knockdown of Rnf114. Knockdown of Cbx5 or Tab1 in maternal RNF114-depleted embryos partially rescued developmental arrest and the defect of major ZGA. In summary, our study reveals that maternal RNF114 plays a precise role in degrading some important substrates during the MZT, the misregulation of which may impede the appropriate activation of major ZGA in mouse embryos.

A General Strategy toward Self-assembled Nanovaccine Based on Cationic Lentinan to Induce Potent Humoral and Cellular Immune Responses.

Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self-assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self-assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll-like receptors 2/4 (TLR2/4) to produce effective antigen cross-presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA-specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid-inducible gene I (RIG-I) receptor, and cytokine-cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)-expressing B16 melanoma cell (B16-OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self-assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system.

Multi-objective and multi-solution source mask optimization using NSGA-II for more direct process window enhancement.

Source and mask optimization (SMO) technology is increasingly relied upon for resolution enhancement of photolithography as critical dimension (CD) shrinks. In advanced CD technology nodes, little process variation can impose a huge impact on the fidelity of lithography. However, traditional source and mask optimization (SMO) methods only evaluate the imaging quality in the focal plane, neglecting the process window (PW) that reflects the robustness of the lithography process. PW includes depth of focus (DOF) and exposure latitude (EL), which are computationally intensive and unfriendly to gradient-based SMO algorithms. In this study, we propose what we believe to be a novel process window enhancement SMO method based on the Nondominated Sorting Genetic Algorithm II (NSGA-II), which is a multi-objective optimization algorithm that can provide multiple solutions. By employing the variational lithography model (VLIM), a fast focus-variation aerial image model, our method, NSGA-SMO, can directly optimize the PW performance and improve the robustness of SMO results while maintaining the in-focus image quality. Referring to the simulations of two typical patterns, NSGA-SMO showcases an improvement of more than 20% in terms of DOF and EL compared to conventional multi-objective SMO, and even four times superior to single-objective SMO for complicated patterns.

Correlation between immune-related adverse events and efficacy of PD-(L)1 inhibitors in small cell lung cancer: a multi-center retrospective study.

BACKGROUND: Patients receiving PD-(L)1 inhibitors frequently encounter unusual side effects known as immune-related adverse events (irAEs). However, the correlation of irAEs development with clinical response in small cell lung cancer (SCLC) is unknown. METHOD: This retrospective study enrolled 244 stage IV SCLC patients who receiving PD-(L)1 inhibitors from 3 cancer centers. The correlation of irAEs with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: 140 in 244 (57%) patients experienced irAEs, with 122 (87.1%) experiencing one and 18 (12.9%) experiencing two or more. Compared to patient without irAEs, those developing irAEs had higher ORR (73.6% vs. 52.9%, P < 0.001) and DCR (97.9% vs. 79.8%, P < 0.001), as well as prolonged median PFS (8.8 vs. 4.5 months, P < 0.001) and OS (23.2 vs. 21.6 months, P < 0.05). Among the different spectra of irAEs, thyroid dysfunction, rash, and pneumonitis were the most powerful indicator for improved PFS. When analyzed as a time-dependent covariate, the occurrence of irAEs was associated with significant improvement in PFS rather than in OS. Furthermore, patients experiencing multisystem irAEs displayed a longer PFS and OS compared with single-system irAEs and the irAE-free ones. IrAEs grade and steroid use did not impact the predictive value of irAEs on PFS. CONCLUSION: The presence of irAEs predicts superior clinical benefit in SCLC. Patients who develop multi-system irAEs may have an improved survival than those developed single-system irAEs and no-irAEs. This association persists even when systemic corticosteroids were used for irAEs management.

Ursonic acid from medicinal herbs inhibits PRRSV replication through activation of the innate immune response by targeting the phosphatase PTPN1.

Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), has caused substantial economic losses to the global swine industry due to the lack of effective commercial vaccines and drugs. There is an urgent need to develop alternative strategies for PRRS prevention and control, such as antiviral drugs. In this study, we identified ursonic acid (UNA), a natural pentacyclic triterpenoid from medicinal herbs, as a novel drug with anti-PRRSV activity in vitro. Mechanistically, a time-of-addition assay revealed that UNA inhibited PRRSV replication when it was added before, at the same time as, and after PRRSV infection was induced. Compound target prediction and molecular docking analysis suggested that UNA interacts with the active pocket of PTPN1, which was further confirmed by a target protein interference assay and phosphatase activity assay. Furthermore, UNA inhibited PRRSV replication by targeting PTPN1, which inhibited IFN-ß production. In addition, UNA displayed antiviral activity against porcine epidemic diarrhoea virus (PEDV) and Seneca virus A (SVA) replication in vitro. These findings will be helpful for developing novel prophylactic and therapeutic agents against PRRS and other swine virus infections.

Identification of B-cell epitopes located on the surface in the PB2 protein of the H9N2 subtype avian influenza virus.

Avian influenza (AI), caused by H9N2 subtype avian influenza virus (AIV), poses a serious threat to poultry farming and public health due to its transmissibility and pathogenicity. The PB2 protein is a major component of the viral RNA polymerase complex. It is of great importance to identify the antigenic determinants of the PB2 protein to explore the function of the PB2 protein. In this study, the PB2 sequence of H9N2 subtype AIV, from 1090 to 1689 bp, was cloned and expressed. The recombinant PB2 protein with cutting gel was used to immunize BALB/c mice. After cell fusion, the hybridoma cell lines secreting monoclonal antibodies (mAbs) targeting the PB2 protein were screened by indirect ELISA and western blotting, and the antigenic epitopes of mAbs were identified by constructing truncated overlapping fragments in the PB2 protein of H9N2 subtype AIV. The results showed that three hybridoma cell lines (4B7, 4D10, and 5H1) that stably secreted mAbs specific to the PB2 protein were screened; the heavy chain of 4B7 was IgG2α, those of 4D10 and 5H1 were IgG1, and all three mAbs had kappa light chain. Also, the minimum B-cell epitope recognized was 475LRGVRVSK482 and 528TITYSSPMMW537. Homology analysis showed that these two epitopes were conserved among the different subtypes of AIV strains and located on the surface of the PB2 protein. The above findings provide an experimental foundation for further investigation of the function of the PB2 protein and developing monoclonal antibody-based diagnostic kits.

First Report of Alternaria alternata Causing Leaf Spot on Oenothera biennis in China.

Oenothera biennis is a versatile plant that can be used for both ornamental and medicinal purposes. Its potential in treating a range of diseases is noteworthy and has been studied extensively (Bayles et al. 2009). In September 2022, leaf spot on O. biennis was first observed in a 0.2 ha plant experimental demonstration land in Libo County (25°23'24″N, 108°4'22″E), Guizhou Province, China. The incidence of all O. biennis was about 60% over the 0.2 ha surveyed. Initially, red round or irregular spots appeared on the leaves, which then gradually turned dry yellow. To identify the cause, diseased tissues (5 mm2) from the margin of the lesions were surface disinfected by immersion in 75% ethanol for 30 sec, and 7% sodium hypochlorite for 1 min, and then rinsed three times with sterile distilled water (Sun et al. 2022). The tissues were cultured in potato dextrose agar (PDA) at 25℃. After 7 days, further purification was performed by transferring onto the new PDA and potato carrot agar (PCA) by single-spore isolation. After 8 days, the colonies on PDA were 80 mm in diameter, cotton-like in texture, dark green in color and nearly circular in shape with a white edge. The conidia on the PCA were short-chains, pear-shaped or oval, pale brown, smooth surface, 15.3-30.8 × 8.3-12.6µm (n = 150). Beaks were columnar or conical, 0-6.0 × 0-4.0µm (n = 100). Conidiophores were solitary straight or flexuous less branched, dark brown, and measured 14.0-60.5 × 3.0-4.5µm. Based upon morphological observations, all these characteristics were consistent with those of Alternaria alternata (Simmons 2007). To further identify the fungal species, internal transcribed spacer (ITS) rDNA regions, glyceraldehyde-3-phosphate dehydrogenase (gpd), Alternaria major allergen (Alt a 1), RNA polymerase second largest subunit gene (RPB2) and translation elongation factor 1-alpha (TEF 1) were amplified and sequenced using the primers ITS4/ITS5, RPB2-5F/RPB2-7CR, gpd1/gpd2, EF1-728F/EF1-986R, and Alt-for/Alt-rev (Woudenberg et al. 2015). Sequences were deposited in GenBank (ITS: OM319523; RPB2: OM849249; gpd: OM296248; TEF1: OM238124; Alt a 1: OM649813). The similarity of the representative isolate YJC and the type strain CBS 595.93 (ITS: KP124320; RPB2: KP124788; gpd: KP124175; TEF1: KP125096; Alt a 1: JQ646399) on the phylogenetic tree was 98%. Therefore, the fungus was identified as A. alternata by morphology and phylogenetic analysis. To confirm pathogenicity, a spore suspension (1 × 106 conidia/ml) of the representative isolate YJC was sprayed on the leaves of six healthy plants and six plants sprayed with distilled water as controls. The plants used in the experiment were covered with plastic bags for 48 h (Luo et al. 2012). After 8 days, all inoculated plants exhibited symptoms of the disease, while the control plants remained symptom-free. The experiment was conducted twice using the same approach. The fungus that has been inoculated was reisolated from the leaves of the infected plants and identified as A. alternata through morphological observation, thus fulfilling Koch's postulates. To the best of our knowledge, this is the first documented case of O. biennis leaf spot caused by A. alternata. This pathogen could pose a threat to O. biennis yield and result in economic losses. For further development of specific control measures, it is important to confirm the identity.

First Report of Alternaria alternata Causing Leaf Blight on Elsholtzia ciliata in China.

Elsholtzia ciliata is an annual medicinal plant characterized to the family Lamiaceae Martinov. It is grown in most parts of China and has high economic value as a traditional Chinese medicine. In September of 2022, E. ciliata plants located at the planting base of traditional Chinses medicine in Daying county (30°35'40″N, 105°14 12″E), Sichuan Province, China, were recorded with leaf blight. The incidence of symptomatic plants was 15% (30 infected plants out of 200 surveyed). The symptoms included an irregular necrotic lesion at the tip of the leaf, which gradually expanded across the entire leaf. To elucidate the cause of the symptoms, 12 symptomatic leaves were sampled from four different plants and 5×5 mm section, including symptomatic and non-symptomatic tissue was excised. Tissue samples were disinfected in 75% ethanol for 30s, and 7% sodium hypochlorite for 1 min, and then rinsed three times with sterile distilled water (Sun et al. 2022). The sampled tissues were placed onto potato dextrose agar (PDA) and incubated at 25℃ in the dark. Seven days later, single spores were recovered onto fresh PDA (Zhu et al. 1992). Colonies on PDA initially appeared white, developing grayish-green conidia with white margins. Conidia (n=150) were collected and observed under the microscope. The conidia were smooth walled and dark brown, with pear-shaped, 12.1-31.4 × 5.0-9.4µm, with 3-5 transverse septa, 1-3 longitudinal or oblique septa. Conidiophores were thick, dark brown, simple with multiple conidial scars, 5.0-75.5 × 2.5.0-5.0µm. Based on morphological observations the 12 isolates were most similar to Alternaria alternata (Simmons 2007). The internal transcribed spacer (ITS) rDNA regions, glyceraldehyde-3-phosphate dehydrogenase (gpd), Alternaria major allergen (Alt a 1), RNA polymerase second largest subunit gene (RPB2) and translation elongation factor 1-alpha (TEF 1) were amplified and sequenced using the primers ITS4/ITS5, RPB2-5F/RPB2-7CR, gpd1/gpd2, EF1-728F/EF1-986R, and Alt-for/Alt-rev respectively (Woudenberg et al. 2015). The sequences of representative isolate (XR) were uploaded in GenBank (ITS: OM319521, RPB2: OM849248, gpd: OM296240, TEF1: OM238122, and Alt a 1: OM649814). The bootstrap value of the isolate and the type strain CBS 595.93 (ITS: KP124320, RPB2: KP124788, gpd: KP124175, TEF1: KP125096, and Alt a 1: JQ646399) on the phylogenetic tree was 99%. Therefore, based on morphology and phylogenetic analysis the fungus was identified as A. alternata. To verify pathogenicity, a spore suspension (1 × 106 conidia/ml) of the representative isolate XR was misted onto the foliage of six twenty-day-old non-symptomatic plants. Six additional plants were sprayed with distilled water and used as controls. The plants were covered with plastic bags for 48 h and incubated at a temperature of 28℃ in the dark. Eight days later, all inoculated plants demonstrated similar symptoms as recorded on the original source, while the control plants were symptomless. The experiment was repeated three times with similar results. A. alternata was re-isolated from the artificially inoculated plants, hence fulfilling Koch's postulates. To our best knowledge this is the first report of leaf blight caused by A. alternata in China on E. ciliate. The disease may be an economic threat and should be further monitored and studied.

Effects of RNA methylation on Tumor angiogenesis and cancer progression.

Tumor angiogenesis plays vital roles in the growth and metastasis of cancer. RNA methylation is one of the most common modifications and is widely observed in eukaryotes and prokaryotes. Accumulating studies have revealed that RNA methylation affects the occurrence and development of various tumors. In recent years, RNA methylation has been shown to play an important role in regulating tumor angiogenesis. In this review, we mainly elucidate the mechanisms and functions of RNA methylation on angiogenesis and progression in several cancers. We then shed light on the role of RNA methylation-associated factors and pathways in tumor angiogenesis. Finally, we describe the role of RNA methylation as potential biomarker and novel therapeutic target.

Extracellular vesicles remodel tumor environment for cancer immunotherapy.

Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged as therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations in the quantity and composition of extracellular vesicles (EVs) contribute to the remodeling of the immune-suppressive tumor microenvironment (TME), thereby influencing the efficacy of immunotherapy. This revelation has sparked clinical interest in utilizing EVs for immune sensitization. In this perspective article, we present a comprehensive overview of the origins, generation, and interplay among various components of EVs within the TME. Furthermore, we discuss the pivotal role of EVs in reshaping the TME during tumorigenesis and their specific cargo, such as PD-1 and non-coding RNA, which influence the phenotypes of critical immune cells within the TME. Additionally, we summarize the applications of EVs in different anti-tumor therapies, the latest advancements in engineering EVs for cancer immunotherapy, and the challenges encountered in clinical translation. In light of these findings, we advocate for a broader understanding of the impact of EVs on the TME, as this will unveil overlooked therapeutic vulnerabilities and potentially enhance the efficacy of existing cancer immunotherapies.

Trends and Projections of Stomach Cancer Incidence in Hong Kong: A Population-Based Study.

OBJECTIVES: The burden of stomach cancer remains high in Hong Kong. We sought to evaluate the associations of age, period, and birth cohort with the changing trend in the incidence of stomach cancer and to provide projections through 2030. MATERIALS AND METHODS: We performed an age-period-cohort analysis and projections up to 2030 using data from the Hong Kong Cancer Registry. Additionally, we used a population decomposition algorithm to assess the drivers in the number of incident cases of stomach cancer in Hong Kong. RESULTS: Among the 26,813 stomach cancer patients, from 1994 to 2018, the age-standardized incidence rate of stomach cancer decreased for both sexes. The incidence increased with age and was highest for those aged 85 years or older. Period relative risk (RR) showed a monotonic decreasing pattern throughout the study period for both sexes before 2010. Cohort RR for males was monotonically decreasing but changed little after the 1967-1971 birth cohort. In contrast, cohort RR for females declined in the pre-1927-1931 birth cohort but slowed down since. It is projected that there will be 906 male patients and 954 female patients in 2030. Decomposition analysis suggested that population growth and aging were associated with substantial changes in the number of incident cases of stomach cancer in Hong Kong. CONCLUSIONS: Both period and cohort risk of developing stomach cancer in Hong Kong have slowed down or plateaued. Our study demonstrates that population aging and growth are the main drivers of the increased number of incident cases of stomach cancer in Hong Kong.

Changing patterns of nasopharyngeal carcinoma incidence in Hong Kong: a 30-year analysis and future projections.

BACKGROUND: This study aims to evaluate the relationship between age, period, and birth cohort with the incidence trends of Nasopharyngeal Carcinoma (NPC) in Hong Kong, make projections through 2030 and parse the drivers of the incidence. METHODS: Using data from the Hong Kong Cancer Registry, we used an age-period-cohort model to uniquely estimate age, period, and cohort effects on NPC incidence trends and make projections. We further assessed the drivers of NPC incidence using a validated decomposition algorithm. RESULTS: From 1991 to 2020, crude and age-standardized incidence rates of NPC decreased significantly. The net drifts showed significant downward trends for both sexes, and local drift declined in all age groups. Period and cohort rate ratios revealed monotonic declining patterns for both sexes. Projections suggested that NPC incidence will continue to decline. Population decomposition showed that while population growth and ageing have led to an increase in NPC cases, epidemiologic changes offset these increases, resulting in an encouraging downward trend in the incidence and new NPC cases in Hong Kong. CONCLUSIONS: The period and cohort risk of NPC in Hong Kong decreased, and epidemiologic changes offset the contribution of demographic factors, resulting in a continued decline in NPC incidence and cases.

First Report of Alternaria Leaf Blight Caused by Alternaria alternata on Agrimonia pilosa in China.

Agrimonia pilosa is widely distributed in East Asian countries, including China, Japan, Korea and Mongolia. It is a common medicinal plant with pharmacological effects such as procoagulant, antioxidant, anti-inflammatory. In September 2022, leaf blight was the first time observed on A. pilosa in a 2.6-ha A. pilosa plantation in Harbin, Heilongjiang Province, China. The incidence of the disease reached 80%, and almost every leaf had symptoms. Initially, yellow-to-brown spots appeared on the tips or edges of the leaves. As the disease progressed, the lesions gradually enlarged and merged. Finally, the whole leaf withered. To identify the causal agent, twenty symptomatic leaves were arbitrarily collected from ten diseased plants. Diseased leaf pieces that measured 5 mm2 were disinfested in 75% ethyl alcohol for 30 s and 7% NaOCl for 60 s, rinsed three times in sterile distilled water (Sun et al. 2022), and placed on potato dextrose agar (PDA). Ten fungal isolates obtained by single-spore isolations were selected for further study. Colonies of these isolates on PDA were off-white to black with abundant cotton-like aerial hyphae, and the colony diameter was 75 to 90 mm. The isolates produced conidia that were ovate to nearly oval, gray-to-black, with 1 to 4 transverse septa and 0 to 2 oblique septa, smooth surfaced, parietal cells extending into the beak, and measured 15.0 to 35.5 × 6.0 to 13.0 µm. Conidiophores were taupe, erect or curved, branched, with pronounced spore marks. All ten fungal isolates were morphologically similar to Alternaria alternata (Simmons 2007). Two representative isolates LYC and LYC01 were used for molecular identification. The internal transcribed spacer (ITS) region, RNA polymerase second largest subunit (RPB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), translation elongation factor 1-alpha (TEF1), and Alternaria major allergen (Alt a 1) were amplified with the primers ITS4/ITS5(White et al. 1990), RPB2-5F2/RPB2-7CR (Khodaei and Arzanlou 2013), gpd1/gpd2, EF1-728F/EF1-986R (Sun et al. 2023) and Alt-for/Alt-rev (Woudenberg et al. 2015). The resulting sequences were deposited in GenBank (ITS, OM319510, OQ788347; RPB2, OM296263, OQ862336; GAPDH, OM296236, OQ862337; TEF1, OM238113, OQ862338; Alta1, OM171260, OQ862339). Phylogenetic analyses showed 100% identity between LYC and LYC01 and the type strain CBS 121456. Thus, the fungus was identified as A. alternata based on morphology and molecular analysis. Pathogenicity tests were done by spraying conidial suspensions containing 106 conidia/ml of A. alternata isolates LYC and LYC01 on leaves of six healthy A. pilosa plants, separately. Another six plants were sprayed with sterile distilled water as control. Both groups of plants were covered with plastic bags and placed in a greenhouse maintained at 25° C. Plastic bags were removed from plants after 48 h. Fifteen days later, the disease symptoms on the inoculated plants were similar to those observed in the original sample, whereas the control plants remained healthy. The pathogenicity tests were conducted three times. The strains of A. alternata were reisolated from the symptomatic inoculated plants, confirming Koch's postulates. To our knowledge, this is the first report of A. alternata causing leaf blight on A. pilosa in China. Identifying the agent responsible for the disease can help with disease control and plant management in the field.

Advances in mitochondrial DNA base editing technology.

Mitochondria, the energy factories of higher eukaryotes, provide energy (ATP) for life activities through aerobic respiration. They possess their own genome, mitochondrial DNA (mtDNA), which encodes 37 genes. Mutations in mtDNA cause mitochondrial diseases, and more than 100 pathogenic mutations have been identified in human mtDNA, with a total incidence rate of about 1/5000. In recent years, advances in CRISPR-based base editing technology have enabled accurate editing of nuclear genes. However, it remains a challenge to achieve precise base editing on mtDNA due to the difficulty of guide RNA in the CRISPR system passing through the mitochondrial double-membrane. In 2020, David R. Liu's group at Harvard University reported a double-stranded DNA deaminase DddA from Burkholderia cenocepacia, which was fused with the programmable transcription activator-like effector (TALE) and uracil glycosylase inhibitor (UGI) to develop DddA-derived cytosine base editors (DdCBEs). Using DdCBEs, they were able to achieve specific and efficient C?G to T?A conversion on mtDNA for the first time. In this review, we summarize the recent progress of mitochondrial base editing technology based on DddA and prospect its future application prospects. The information presented may facilitate interested researchers to grasp the principles of mitochondrial base editing, to use relevant base editors in their own studies, or to optimize mitochondrial base editors in the future.

Global optimisation of source and mask in inverse lithography via tabu search combined with genetic algorithm.

Source mask optimisation (SMO) is a resolution enhancement technology that is utilised in the advanced process node of optical lithography to achieve acceptable imaging quality and fidelity. It is crucial in enhancing the convergence performance and optimisation capability of pixel-based SMO. In this study, an SMO approach that employs a genetic algorithm (GA), combined with the tabu search method (TS), is proposed. GA-TS, a hybrid-type global optimisation algorithm, has an outperforming capacity to avoid local optima owing to the excellent local searching function of TS. Furthermore, an edge-optimisation strategy was implemented to optimise the mask for a low-complexity mask layout. The simulation results confirm that the proposed approach exhibits exceptional optimisation capability and convergence performance.

A Low-Latency RDP-CORDIC Algorithm for Real-Time Signal Processing of Edge Computing Devices in Smart Grid Cyber-Physical Systems.

Smart grids are being expanded in scale with the increasing complexity of the equipment. Edge computing is gradually replacing conventional cloud computing due to its low latency, low power consumption, and high reliability. The CORDIC algorithm has the characteristics of high-speed real-time processing and is very suitable for hardware accelerators in edge computing devices. The iterative calculation method of the CORDIC algorithm yet leads to problems such as complex structure and high consumption of hardware resource. In this paper, we propose an RDP-CORDIC algorithm which pre-computes all micro-rotation directions and transforms the conventional single-stage iterative structure into a three-stage and multi-stage combined iterative structure, thereby enabling it to solve the problems of the conventional CORDIC algorithm with many iterations and high consumption. An accuracy compensation algorithm for the direction prediction constant is also proposed to solve the problem of high ROM consumption in the high precision implementation of the RDP-CORDIC algorithm. The experimental results showed that the RDP-CORDIC algorithm had faster computation speed and lower resource consumption with higher guaranteed accuracy than other CORDIC algorithms. Therefore, the RDP-CORDIC algorithm proposed in this paper may effectively increase computation performance while reducing the power and resource consumption of edge computing devices in smart grid systems.

Four new fatty acid derivatives from Diaporthe sp. T24, an endophytic fungus isolated from Ligularia fischer.

The endophytic fungus Diaporthe sp. is known to contain many secondary metabolites, but fatty acid derivatives have rarely been found. In this study, four new fatty acid derivatives (1-4), together with four known compounds (5-8), were isolated from Diaporthe sp., which was obtained from the stem of Ligularia fischeri. The absolute configurations of the new compounds 1-4 were deduced based on spectroscopic technique and J-based coupling constant analysis. Moreover, compound 1 exhibited cytotoxic activities against HCT-8 and MCF-7 cancer cells, and compounds 3 and 4 showed modest selectivity for HCT-8 cells by MTT assay.

Numerical Investigation of Exergy Loss of Ammonia Addition in Hydrocarbon Diffusion Flames.

In this paper, a theoretical numerical analysis of the thermodynamics second law in ammonia/ethylene counter-flow diffusion flames is carried out. The combustion process, which includes heat and mass transfer, as well as a chemical reaction, is simulated based on a detailed chemical reaction model. Entropy generation and exergy loss due to various reasons in ammonia/ethylene and argon/ethylene flames are calculated. The effects of ammonia addition on the thermodynamics efficiency of combustion are investigated. Based on thermodynamics analysis, a parameter, the lowest emission of pollutant (LEP), is proposed to establish a relationship between the available work and pollutant emissions produced during the combustion process. Chemical reaction paths are also analyzed by combining the chemical entropy generation, and some important chemical reactions and substances are identified. The numerical results reveal that ammonia addition has a significant enhancement on heat transfer and chemical reaction in the flames, and the total exergy loss rate increases slightly at first and then decreases with an increase in ammonia concentration. Considering the factors of thermodynamic efficiency, the emissions of CO2 and NOx reach a maximum when ammonia concentration is near 10% and 30%, respectively. In terms of the chemical reaction path analysis, ammonia pyrolysis and nitrogen production increase significantly, while ethylene pyrolysis and carbon monoxide production decrease when ammonia is added to hydrocarbon diffusion flames.

Depletion of m6 A reader protein YTHDC1 induces dilated cardiomyopathy by abnormal splicing of Titin.

N6 -methyladenosine (m6 A) is the most prevalent modification in mRNA and engages in multiple biological processes. Previous studies indicated that m6 A methyltransferase METTL3 ('writer') and demethylase FTO ('eraser') play critical roles in heart-related disease. However, in the heart, the function of m6 A 'reader', such as YTH (YT521-B homology) domain-containing proteins remains unclear. Here, we report that the defect in YTHDC1 but not other YTH family members contributes to dilated cardiomyopathy (DCM) in mice. Cardiac-specific conditional Ythdc1 knockout led to obvious left ventricular chamber enlargement and severe systolic dysfunction. YTHDC1 deficiency also resulted in the decrease of cardiomyocyte contractility and disordered sarcomere arrangement. By means of integrating multiple high-throughput sequence technologies, including m6 A-MeRIP, RIP-seq and mRNA-seq, we identified 42 transcripts as potential downstream targets of YTHDC1. Amongst them, we found that Titin mRNA was decorated with m6 A modification and depletion of YTHDC1 resulted in aberrant splicing of Titin. Our study suggests that Ythdc1 plays crucial role in regulating the normal contractile function and the development of DCM. These findings clarify the essential role of m6 A reader in cardiac biofunction and provide a novel potential target for the treatment of DCM.

Epithelial-mesenchymal transition induced cancer-stem-cell-like characteristics in hepatocellular carcinoma.

Hepatocellular carcinoma in China accounts for half of the world's incidence. Both epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are thought to be involved in tumor malignant progression. However, the relationship between EMT and CSCs is still unclear. Bioinformatics analysis was performed to evaluate the relationship between EMT and CSCs. The EMT and CSC regulatory mechanism was investigated through Transwell, wound-healing, sphere formation, colony-forming, and western blotting assays. Immunofluorescence and immunoprecipitation were used to study the interaction of hypoxia inducible factor 1α (HIF-1α) /Notch1. Immunohistochemical study was applied to investigate the expression pattern in the process of hepatocellular carcinogenesis and development. In our present study, bioinformatics results indicate that the expression of EMT-related molecules is correlated with CSCs. In vitro studies indicated that EMT activation could induce CSC characteristics. Notch1 was confirmed to mediate the process of EMT-induced CSCs through the interaction with HIF-1α directly. Our findings indicate that EMT could induce CSC-like characteristics, which is mediated by HIF-1α-upregulated Notch intracellular domain expression.